Oxidative stress causes bone loss in estrogen-deficient mice through enhanced bone marrow dendritic cell activation

Francesco Grassi, Gianluca Tell, Michaela Robbie-Ryan, Yuhao Gao, Masakazu Terauchi, Xiaoying Yang, Milena Romanello, Dean P. Jones, M. Neale Weitzmann, Roberto Pacifici

Research output: Contribution to journalArticlepeer-review

Abstract

Increased production of tumor necrosis factor α (TNF) in the bone marrow (BM) in response to both oxidative stress and T cell activation contributes to the bone loss induced by estrogen deficiency, but it is presently unknown whether oxidative stress causes bone loss through T cells. Here we show that ovariectomy causes an accumulation in the BM of reactive oxygen species, which leads to increased production of TNF by activated T cells through upregulation of the costimulatory molecule CD80 on dendritic cells. Accordingly, bone loss is prevented by treatment of ovariectomized mice with either antioxidants or CTLA4-Ig, an inhibitor of the CD80/CD28 pathway. In summary, reactive oxygen species accumulation in the BM is an upstream consequence of ovariectomy that leads to bone loss by activating T cells through enhanced activity of BM dendritic cells, and these findings suggest that the CD80/CD28 pathway may represent a therapeutic target for postmenopausal bone loss.

Original languageEnglish
Pages (from-to)15087-15092
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume104
Issue number38
DOIs
Publication statusPublished - Sep 18 2007

Keywords

  • CTLA-4Ig
  • Osteoporosis
  • Reactive oxygen species
  • T cells
  • Tumor necrosis factor

ASJC Scopus subject areas

  • Genetics
  • General

Fingerprint Dive into the research topics of 'Oxidative stress causes bone loss in estrogen-deficient mice through enhanced bone marrow dendritic cell activation'. Together they form a unique fingerprint.

Cite this